Live-animal imaging of native hematopoietic stem and progenitor cells
| Autor: | Sergei A. Vinogradov, Negar Seyedhassantehrani, Archibald S. Perkins, Tatiana V. Esipova, Azucena Ramos, Guoji Guo, Charles P. Lin, Raffaele A. Calogero, Joel A. Spencer, Riccardo Panero, Constantina Christodoulou, Stuart H. Orkin, Sarah Rudzinskas, Raphaël Turcotte, Shu-Chi A. Yeh, Timm Schroeder, Konstantinos D. Kokkaliaris, Yi Zhang, Fernando D. Camargo |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Endosteum Multidisciplinary Motility hemic and immune systems single-cell sequencing Biology Article Bone remodeling Cell biology Transplantation 03 medical and health sciences Haematopoiesis 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis medicine Bone marrow Stem cell Progenitor cell |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | The biology of hematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions1,2. Particularly challenging has been the study of dynamic HSC behaviors given that live animal HSC visualization in the native niche still represents an elusive goal in the field. Here, we describe a dual genetic strategy in mice that restricts reporter labeling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow (BM)3–5. We find that this subset of LT-HSCs resides in close proximity to both sinusoidal blood vessels and the endosteal surface. In contrast, multipotent progenitor cells (MPPs) display a broader distance distribution from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in BM niches with the deepest hypoxia and instead are found in similar hypoxic environments as MPPs. In vivo time-lapse imaging reveals that LT-HSCs display limited motility at steady-state. Following activation, LT-HSCs display heterogenous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of BM cavities exhibiting bone-remodeling activities. In contrast, cavities with low bone-resorbing activities do not harbor expanding HSCs. These findings point to a new degree of heterogeneity within the BM microenvironment, imposed by the stages of bone turnover. Overall, our approach enables direct visualization of HSC behaviors and dissection of heterogeneity in HSC niches. |
| Databáze: | OpenAIRE |
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